Aims: In the early 1990's, The National Cancer Institute proposed a prospective study of cancer incidence in a cohort of an anticipated 75,000 licensed pesticide applicators and their spouses. Their main purpose was to confirm the link between pesticide exposure and cancer in a study that would be large enough to establish risks related to specific pesticides and evaluate the influence of other known cancer risk factors. Using a prospective design to document exposures before the occurrence of disease, they hoped to avoid the pitfalls inherent in retrospective assessment of pesticide exposure. The promise of detailed assessment of exposures - both occupationally and in the home environment - made this study especially attractive. The NIEHS Epidemiology Branch joined forces with the NCI to study non-cancer health effects in the cohort. Procedures and techniques: Licensed pesticide applicators from North Carolina and Iowa were recruited at the time of license renewal. Applicators completed a short enrollment questionnaire on farming, exposure to pesticides, and lifestyle factors. Applicators who completed the questionnaire were given a set of take-home questionnaires, including two to be completed by the female spouse of farmers. Spouses who did not return the mail questionnaires were given a second chance to enroll by telephone. Over 63,5000 private pesticide applicators were eligible to enroll. Of these 82% completed the enrollment questionnaire and 44% provided more detailed data on exposures and health. Over 43,300 spouses of farmer-applicators were identified and 81% of them enrolled in the study. Data on children and reproductive health were provided by 21,000 spouses. Cancer incidence among the applicators, spouses, and children after five years of follow-up is being determined through linkage with the population-based cancer registries in IA and NC. Follow-up computer-assisted telephone interviews are being conducted to update exposure information and to collect information on changes in health status. Questionnaire modules on health status are tailored to the age and gender of the respondent. Women who did not provide reproductive histories at enrollment are given an opportunity to provide that information at follow-up. Buccal-cell samples are being collected for future analyses of gene and environment interactions. In addition, a food frequency questionnaire is returned by mail. Through the efforts of the EPA, in-depth assessment of pesticide exposure is being made for a small sample of farmers (125) and their families in order to validate the questionnaires and facilitate exposure classification. Both environmental and biological samples are being collected. We also recruited 1,100 current and former African American farmers through churches in five counties in NC to supplement the number of African Americans in the cohort. These farmers are older and were not licensed applicators. Men who were enrolled this way were recently re-interviewed and invited to participate in a study that included the collection of a blood sample to assess DDE levels, hormones, and lipids. Accomplishments: Enrollment has been completed and we are now in the second year of five-year follow-up interviews. To date, completion rates are about 72% for applicators and 83% for spouses. Some of those classified as non-responders in NC were never reached, possibly because they were displaced from their farms during the flooding following Hurricane Floyd. Current efforts to trace and contact these farmers should help to improve response rates. The cohort has been traced through state motor vehicle records, department of agriculture records, social security death tapes, and IRS records to determine losses to follow-up due to moves out of state, and linked with the National Death Index, state vital statistics, and the cancer registries in NC, IA, and neighboring states to determine death rates and cancer incidence. Preliminary analysis of cancer incidence confirms that farmers, as a whole, are healthier than the general US population. There were, however, increases in risk for some specific cancers. These leads are now being pursued with more focused nested studies of specific risk factors. We have used baseline data in descriptive analyses of the cohort. We found for, example, that although we expected to find that contrary to expectation, African American were not more highly exposed to pesticides than were whites. While this may be true of African American farmers overall, those licensed to apply pesticides reported lower lifetime pesticide use and less frequent use of high exposure methods, although they were less likely to use some forms of protective equipment. We also explored factors related to accidental spills and other "high pesticide exposure events" which may identify subgroups at especially high risk for adverse health events. These exploratory analyses led to the inclusion of more detailed questions on pesticide spills in the follow-up questionnaires. In addition, with the collaboration of investigators from the University of Iowa, a nested case-control study of farm accidents and pesticide poisonings was conducted. As a preliminary step in studying links between farm exposures and adverse reproductive events, we examined factors related to menstrual cycle characteristics. We found, for example, that long or irregular cycles were associated with increasing age, increasing body mass index, and late age at menarche. Cycle characteristics were also affected by medical history and in turn related to reproductive outcomes such as infertility and spontaneous abortion risk. We also have used the cross-sectional data to explore factors related to asthma and other respiratory diseases. Self-reported wheeze (an indicator of asthma) was associated with several farm characteristics including contact with animals, grain production, and use of specific chemicals. We compared self-reported information on pesticide use, lifestyle, and demographics for a sample of IA applicators who completed the enrollment questionnaire twice, one year apart. Percent agreement for ever/never use of specific pesticides and application practices was quite high, generally ranging from70% to over 90% and did not vary by education level or other factors. Agreement was lower (50% to 60%) for duration, frequency, or decade of first use of specific pesticides. Level of agreement regarding pesticides was similar to that generally found for diet, exercise, and medical conditions which have been successfully evaluated in many epidemiologic studies. We also assessed bias in the reporting of reproductive health outcomes among a random sample of young wives and found that despite a high level of non-response for some variables, the actual amount of bias was small. We completed follow-up telephone interviews and obtained a blood sample from 137 of the African American men who had been recruited through African American churches. Plasma DDE was found to increase with age and years of farming (two variables that are highly correlated) and was associated with working with cotton and self-reported exposure to DDT. DDE was not associated with hormone levels except among the oldest men.